DNA Damage Response and Inflammatory Signaling Limit the MLL-ENL-Induced Leukemogenesis In Vivo

Takacova S, Slany R, Bartkova J, Stranecky V, Dolezel P, Luzna P, Bartek J, Divoky V (2012)

Publication Status: Published

Publication Type: Journal article, Original article

Publication year: 2012

Journal

Cancer Cell Elsevier (Cell Press)

Book Volume: 21

Pages Range: 517-531

Journal Issue: 4

DOI: 10.1016/j.ccr.2012.01.021

Abstract

Activation of the MLL-ENL-ERtm oncogene initiates aberrant proliferation of myeloid progenitors. Here, we show induction of a fail-safe mechanism mediated by the DNA damage response (DDR) machinery that results in activation of the ATR/ATM-Chk1/Chk2-p53/p21 checkpoint and cellular senescence at early stages of cellular transformation caused by a regulatable MLL-ENL-ERtm in mice. Furthermore, we identified the transcription program underlying this intrinsic anticancer barrier, and DDR-induced inflammatory regulators that fine-tune the signaling toward senescence, thereby modulating the fate of MLL-ENL-immortalized cells in a tissue-environment-dependent manner. Our results indicate that DDR is a rate-limiting event for acquisition of stem cell-like properties in MLL-ENL-ERtm-mediated transformation, as experimental inhibition of the barrier accelerated the transition to immature cell states and acute leukemia development. © 2012 Elsevier Inc.

Authors with CRIS profile

Robert Slany Lehrstuhl für Genetik

Involved external institutions

Palacky University Olomouc / Univerzita Palackého v Olomouci CZ Czech Republic (CZ) Danish Cancer Society Research Center DK Denmark (DK) Univerzita Karlova v Praze / Charles University in Prague CZ Czech Republic (CZ)

How to cite

APA:

Takacova, S., Slany, R., Bartkova, J., Stranecky, V., Dolezel, P., Luzna, P.,... Divoky, V. (2012). DNA Damage Response and Inflammatory Signaling Limit the MLL-ENL-Induced Leukemogenesis In Vivo. Cancer Cell, 21(4), 517-531. https://doi.org/10.1016/j.ccr.2012.01.021

MLA:

Takacova, Sylvia, et al. "DNA Damage Response and Inflammatory Signaling Limit the MLL-ENL-Induced Leukemogenesis In Vivo." Cancer Cell 21.4 (2012): 517-531.

BibTeX: Download